The dysfunction of endothelial progenitor cells (EPCs) is closely associated with diabetic vascular complications. Both glucagonlike peptide-1 receptor (GLP-1R) and silent information regulator 1 (SIRT1) can control systemic glucose homeostasis and protect endothelial cells against hyperglycemia-induced oxidative stress. In this study, we mainly assessed the role played by SIRT1 and GLP-1R and their relationship in regulating the function of late EPCs under hyperglycemia stimulation. Human peripheral blood mononuclear cells (PBMCs) were cultured in EGM-2 medium and induced to differentiate into EPCs and 25 mM glucose was used to stimulate EPCs to obtain a hyperglycemia condition. Subsequently, the expression and location of GLP-1R and SIRT1 in EPCs were detected. After GLP-1R or SIRT1 knockdown, or the treatment by GLP-1R agonist and/or SIRT1 agonist/inhibitor, the effects of SIRT1 and GLP-1R and their relationship in regulating the function of late EPCs under hyperglycemia stimulation was studied by detecting the apoptosis, migration, adhesion and angiogenicity abilities of EPCs. Results demonstrated that, in high-glucose stimulated EPCs, the expression of GLP-1R and SIRT1 was down-regulated. The knockdown of either GLP-1R or SIRT1 could increase EPCs apoptosis and weaken the migration, adhesion and angiogenicity abilities of EPCs. In addition, the improvement effects of Exendin-4 or GLP-1R over-expression on EPCs dysfunction could be weakened to some degree under SIRT1 knockdown. In conclusion, both GLP-1R and SIRT1 expression played important roles in regulating EPCs dysfunction under hyperglycemia and the up-regulation of GLP-1R improved the dysfunction of late EPCs by regulating SIRT1 expression.

内皮祖细胞（EPCs）功能障碍与糖尿病血管并发症密切相关。胰高血糖素样肽 1 受体 (GLP-1R) 和沉默信息调节因子 1 (SIRT1) 均可控制全身葡萄糖稳态并保护内皮细胞免受高血糖诱导的氧化应激。在本研究中，我们主要评估了 SIRT1 和 GLP-1R 在高血糖刺激下调节晚期 EPC 功能的作用及其关系。人外周血单个核细胞 (PBMC) 在 EGM-2 培养基中培养并诱导分化为 EPC，并使用 25 mM 葡萄糖刺激 EPC 以获得高血糖状态。随后，检测了 GLP-1R 和 SIRT1 在 EPCs 中的表达和定位。GLP-1R或SIRT1后通过检测细胞凋亡、迁移、粘附和EPCs的血管生成能力。结果表明，在高糖刺激的 EPCs 中，GLP-1R 和 SIRT1 的表达下调。GLP-1R或SIRT1的敲低可增加EPCs凋亡并削弱EPCs的迁移、粘附和血管生成能力。此外，在SIRT1下，Exendin-4 或GLP-1R过表达对 EPCs 功能障碍的改善作用可能会有所减弱。击倒。综上所述，GLP-1R和SIRT1的表达在调节高血糖下的EPCs功能障碍中发挥了重要作用，GLP-1R的上调通过调节SIRT1的表达改善了晚期EPCs的功能障碍。